Publications by authors named "Neha Rastogi"

52 Publications

Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model.

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA.

Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients. However, no mouse models progressed into heart failure, and dog models showed highly variable progression insufficient to evaluate efficacy of micro-dystrophin or other therapies on DMD heart failure. To overcome this barrier, we have generated the first DMD mouse model to our knowledge that reproducibly progresses into heart failure. This model shows cardiac inflammation and fibrosis occur prior to reduced function. Fibrosis does not continue to accumulate, but inflammation persists after function declines. We used this model to test micro-dystrophin gene therapy efficacy on heart failure prevention for the first time. Micro-dystrophin prevented declines in cardiac function and prohibited onset of inflammation and fibrosis. This model will allow identification of committed pathogenic steps to heart failure and testing of genetic and nongenetic therapies to optimize cardiac care for patients with DMD.
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http://dx.doi.org/10.1172/jci.insight.146511DOI Listing
April 2021

COVID-19 reinfection in two children with cancer.

Pediatr Hematol Oncol 2021 Feb 24:1-4. Epub 2021 Feb 24.

Department of Microbiology, Medanta The Medicity, Gurgaon, Haryana, India.

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http://dx.doi.org/10.1080/08880018.2020.1855276DOI Listing
February 2021

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies.

Transfus Apher Sci 2021 Feb 3:103075. Epub 2021 Feb 3.

Department of Hematology& Bone Marrow Transplantation, Max Superspecialty Hospital, Saket, New Delhi, 110017, India. Electronic address:

Background: Data on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce.

Objective: To study 14-day mortality in patients who received CPT.

Patients & Methods: Retrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed.

Results: The median age of the study cohort was 62 years (18-80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2-25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy.

Conclusions: We provide a large series of patients with hematological malignancies and role of CPT in this group.
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http://dx.doi.org/10.1016/j.transci.2021.103075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857080PMC
February 2021

Multicenter Outcome of Hematopoietic Stem Cell Transplantation for Primary Immune Deficiency Disorders in India.

Front Immunol 2020 8;11:606930. Epub 2021 Jan 8.

Department of Hematology, Christian Medical College, Vellore, India.

Background: Hematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome.

Patients And Methods: We collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival.

Results: A total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%.

Conclusion: Survival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID.
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http://dx.doi.org/10.3389/fimmu.2020.606930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819851PMC
January 2021

Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide for Pediatric Acute Leukemia is Safe and Effective.

J Pediatr Hematol Oncol 2020 Dec 9. Epub 2020 Dec 9.

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, India.

Background: Haploidentical family donor is universally available and is fast emerging as an alternative donor choice for children with leukemia needing hematopoietic stem cell transplant (HSCT). Here we describe our experience of treating children with acute leukemia by haploidentical HSCT with posttransplant cyclophosphamide (PTCy).

Methods: We retrospectively analyzed the outcome data of 17 children with acute leukemia who underwent related haploidentical HSCT. Fifteen were in complete remission (CR) before HSCT: CR1-6, CR2-7, and CR3-2 and 2 were not in remission. Donors were mobilized with granulocyte colony stimulating factor. The conditioning was nonmyeloablative in 4 and myeloablative in 13. All received PTCy 50 mg/kg on days 3 and 4 as graft-versus-host disease (GVHD) prophylaxis along with tacrolimus or cyclosporine and mycophenolate mofetil. A median of 8.94 million of CD34 cells/kg was infused.

Results: All patients were engrafted for neutrophil and platelets, except 1 child with refractory acute myeloid leukemia disease who relapsed before engraftment. Five children relapsed (4 died and 1 child with CD20-positive leukemia is disease free after Rituximab therapy). There was 1 transplant-related mortality due to grade IV GVHD. Remaining 11 patients are in CR. Acute GVHD was seen in 4 patients. Out of 4, 3 children later developed chronic GVHD and all are alive and disease free. Three of 4 children who received nonmyeloablative conditioning have relapsed. Overall survival is 70.5% and event-free survival is 64.7%. Median follow-up of all patients was 393 days.

Conclusion: Haploidentical HSCT with PTCy is a safe and effective therapy for children with acute leukemia. Myeloablative conditioning and chronic GVHD lead to improved disease-free survival.
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http://dx.doi.org/10.1097/MPH.0000000000002030DOI Listing
December 2020

Antimicrobial Resistance Patterns in Clinically Significant Isolates from Medical Wards of a Tertiary Care Hospital in North India.

J Lab Physicians 2020 Dec 23;12(3):196-202. Epub 2020 Nov 23.

Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.

 The global burden of infections due to multidrug-resistant organism (MDRO) has a significant impact on patients' morbidity and mortality along with increased healthcare expenditure.  This article estimates the prevalence of MDRO and the spectrum of clinical infectious syndromes caused by these organisms in medical wards of a tertiary care hospital in India.  A cross-sectional observational study was performed among patients admitted in medicine wards diagnosed with the various infectious syndromes and one or more clinically significant positive culture at a tertiary care hospital in North India over a period of 18 months.  Out of 323 clinically significant microbiological culture isolates from 229 patients included in the study, 86 (27%) isolates showed multidrug resistance (MDR) pattern, 197 (61%) isolates showed possible extremely drug-resistance pattern, and only 40 (12%) isolates showed nonmultidrug-resistance pattern of antibiogram.  The prevalence of MRDOs is high in clinically significant culture isolates from medicine wards in India. This emphasizes the importance of appropriate antibiotic usage and implementation of antibiotic stewardship programs in this part of the world.
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http://dx.doi.org/10.1055/s-0040-1721161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684999PMC
December 2020

Haploidentical Stem Cell Transplant With Post Transplant Cyclophosphamide for Chronic Granulomatous Disease With Thiotepa, Busulfan, and Fludarabine as Conditioning.

J Pediatr Hematol Oncol 2020 Nov 23. Epub 2020 Nov 23.

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute Medanta The Medicity Hospital, Gurgaon Haryana, India.

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http://dx.doi.org/10.1097/MPH.0000000000002015DOI Listing
November 2020

Fluoxetine-Induced Acquired Platelet Aggregation Defect: a Rare Cause of Oral Bleeding.

Pediatr Hematol Oncol 2020 Nov 5:1-3. Epub 2020 Nov 5.

Paediatric Hematology Oncology and Bone Marrow Transplantation, Medanta - The Medicity, Gurgaon, India.

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http://dx.doi.org/10.1080/08880018.2020.1836099DOI Listing
November 2020

Muscle Twitch Kinetics Are Dependent on Muscle Group, Disease State, and Age in Duchenne Muscular Dystrophy Mouse Models.

Front Physiol 2020 25;11:568909. Epub 2020 Sep 25.

Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, United States.

Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the lack of functional dystrophin protein. In muscular dystrophy preclinical research, it is pertinent to analyze the force of the muscles affected by the disease to assess pathology and potential effectiveness of therapeutic interventions. Although muscles function at sub-maximal levels , maximal tetanic contractions are most commonly used to assess and report muscle function in muscular dystrophy studies. At submaximal activation, the kinetics of contraction and relaxation are heavily impacted by the kinetics of the single twitch. However, maximal tetanic force is often the main, if not sole, outcome measured in most studies, while contractile kinetics are rarely reported. To investigate the effect of muscle disease on twitch contraction kinetics, isolated diaphragm and (EDL) muscles of 10-, 20-week, "het" (dystrophin deficient and utrophin haplo-insufficient), and 52-week (dystrophin deficient) mice were analyzed and compared to wild-type controls. We observed that twitch contractile kinetics are dependent on muscle type, age, and disease state. Specific findings include that diaphragm from wildtype mice has a greater time to 50% relaxation (RT50) than time to peak tension (TTP) compared to the het and dystrophic models, where there is a similar TTP compared to RT50. Diaphragm twitch kinetics remain virtually unchanged with age, while the EDL from het and mice initially has a greater RT50 than TTP, but the TTP increases with age. The difference between EDL contractile kinetics of dystrophic and wildtype mice is more prominent at young age. Differences in kinetics yielded greater statistical significance compared to previously published force measurements, thus, using kinetics as an outcome parameter could potentially allow for use of smaller experimental groups in future study designs. Although this study focused on DMD models, our findings may be applicable to other skeletal muscle conditions and diseases.
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http://dx.doi.org/10.3389/fphys.2020.568909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545010PMC
September 2020

Upfront Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide in Children With Severe Aplastic Anemia.

J Pediatr Hematol Oncol 2020 11;42(8):500

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute Medanta The Medicity Hospital, Gurgaon Haryana, India.

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http://dx.doi.org/10.1097/MPH.0000000000001957DOI Listing
November 2020

Haploidentical Hematopoietic Stem Cell Transplantation for Relapsed Metastatic Retinoblastoma.

J Pediatr Hematol Oncol 2020 11;42(8):499

Pediatric Hematology Oncology and Bone Marrow Transplant Unit Cancer Institute Medanta The Medicity Hospital, Gurgaon Haryana, India.

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http://dx.doi.org/10.1097/MPH.0000000000001955DOI Listing
November 2020

Mineralocorticoid receptor antagonism by finerenone is sufficient to improve function in preclinical muscular dystrophy.

ESC Heart Fail 2020 Sep 18. Epub 2020 Sep 18.

Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.

Aims: Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 and usually die in the second to third decades of life from cardiac and respiratory failure. Symptomatic treatment includes the use of anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, and increased risk of cardiovascular disease. Novel treatment options include blockade of the renin-angiotensin-aldosterone system, because angiotensin as well as aldosterone contribute to persistent inflammation and fibrosis, and aldosterone blockade represents an efficacious anti-fibrotic approach in cardiac failure. Recent preclinical findings enabled successful clinical testing of a combination of steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on dystrophic skeletal muscle and heart has not been investigated. Here, we tested efficacy of the novel non-steroidal MRA finerenone as a monotherapy in a preclinical DMD model.

Methods And Results: The dystrophin-deficient, utrophin haploinsufficient mouse model of DMD was treated with finerenone and compared with untreated dystrophic and wild-type controls. Grip strength, electrocardiography, cardiac magnetic resonance imaging, muscle force measurements, histological quantification, and gene expression studies were performed. Finerenone treatment alone resulted in significant improvements in clinically relevant functional parameters in both skeletal muscle and heart. Normalized grip strength in rested dystrophic mice treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued finerenone-treated dystrophic mice showed an even greater relative improvement (P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD measured during a contraction-induced injury protocol. Normalized limb muscle force after five lengthening contractions resulted in retention of 71 ± 7% of baseline force in finerenone-treated compared with only 51 ± 4% in untreated dystrophic mice. Finerenone treatment also prevented significant reductions in myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. Moreover, treatment with finerenone led to very specific cardiac gene expression changes in clock genes that might modify cardiac pathophysiology in this DMD model.

Conclusions: Finerenone administered as a monotherapy is disease modifying for both skeletal muscle and heart in a preclinical DMD model. These findings support further evaluation of finerenone in DMD clinical trials.
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http://dx.doi.org/10.1002/ehf2.12996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754779PMC
September 2020

Understanding the true burden of "Naegleria fowleri" (Vahlkampfiidae) in patients from Northern states of India: Source tracking and significance.

Eur J Protistol 2020 Oct 19;76:125726. Epub 2020 Jun 19.

Centre for Biotechnology, Maharishi Dayanand University, Rohtak, India.

The present study is an attempt to investigate the presence of Naegleria fowleri in Indian population. A total of 307 patients were enrolled and water samples were collected from both residential and surrounding areas of patients found positive for N. fowleri. The different species of Naegleria from both clinical and water samples were identified taxonomically. Recommended microbiological conventional techniques were used to identify different Naegleria stages and other free-living amoebae from the samples. PCR assays, using both genus and species specific primers were also optimized. None of the samples were positive by conventional microbiological examinations. However, PCR assays detected only three samples positive for N. fowleri. A total of 10 water bodies (ponds), that were used by Naegleria positive patients were examined. The pH and temperature of the water samples collected from water bodies ranged between 5.6-7.2 and 25-32 °C respectively. Among all the 10 water samples tested, four samples were positive for genus Naegleria by PCR assay, of which only two samples, showed positive amplification for N. fowleri. The sequence analysis of N. fowleri strain belonged to genotype II.
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http://dx.doi.org/10.1016/j.ejop.2020.125726DOI Listing
October 2020

Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide in Wiskott-Aldrich Syndrome With Myeloablative Conditioning.

J Pediatr Hematol Oncol 2021 03;43(2):e230-e233

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, India.

Hematopoietic stem cell transplant (HSCT) is the only curative treatment modality for Wiskott-Aldrich syndrome. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an upcoming option in children with nonmalignant conditions. However, only few cases have been reported for Wiskott-Aldrich syndrome HSCT with PTCy approach. Here we report a 4-year-old boy, treated successfully by haploidentical HSCT with myeloablative conditioning (busulfan, fludarabine, and thiotepa) and PTCy. Posttransplant chimerism was fully donor. Of 13 cases (current case and other 12 published cases) 10 are alive and disease free after haploidentical HSCT with PTCy. Haploidentical HSCT with PTCy using myeloablative conditioning is feasible and safe.
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http://dx.doi.org/10.1097/MPH.0000000000001841DOI Listing
March 2021

Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide for Isolated Central Nervous System Blast Crisis in a Child With Chronic Myeloid Leukemia.

J Pediatr Hematol Oncol 2021 01;43(1):e146-e147

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, India.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder. The extramedullary blast crisis (BC) is a known complication of CML, but it usually accompanies a systemic disease. However, an isolated central nervous system (CNS) BC at relapse is very rare and has a very poor prognosis. Salvage is even more difficult for patients who relapse with a CNS BC after an allogeneic stem cell transplant (SCT). Here, we report successful treatment of an isolated CNS BC of CML in a 14-year-old boy who relapsed with isolated a CNS BC after matched sibling donor SCT by haploidentical SCT with posttransplant cyclophosphamide.
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http://dx.doi.org/10.1097/MPH.0000000000001675DOI Listing
January 2021

Mineralocorticoid Receptor Signaling Contributes to Normal Muscle Repair After Acute Injury.

Front Physiol 2019 25;10:1324. Epub 2019 Oct 25.

Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, United States.

Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and muscle progenitor cells within the muscle microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic muscle injury, but eventually, the regenerative portion of the cycle is disrupted and fibrosis replaces degenerated muscle fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated to increase skeletal muscle function, decrease fibrosis, and directly improve membrane integrity in muscular dystrophy mice, and therefore are being tested clinically. Conditional knockout of MR from muscle fibers in muscular dystrophy mice also improves skeletal muscle function and decreases fibrosis. The mechanism of efficacy likely results from blocking MR signaling by its endogenous agonist aldosterone, being produced at high local levels in regions of muscle damage by infiltrating myeloid cells. Since chronic and acute injuries share the same cellular processes to regenerate muscle, and MR antagonists are clinically used for a wide variety of conditions, it is crucial to define the role of MR signaling in normal muscle repair after injury. In this study, we performed acute injuries using barium chloride injections into muscles both in myofiber MR conditional knockout mice on a wild-type background (MRcko) and in MR antagonist-treated wild-type mice. Steps of the muscle regeneration response were analyzed at 1, 4, 7, or 14 days after injury. Presence of the aldosterone synthase enzyme was also assessed during the injury repair process. We show for the first time aldosterone synthase localization in infiltrating immune cells of normal skeletal muscle after acute injury. MRcko mice had an increased muscle area infiltrated by aldosterone synthase positive myeloid cells compared to control injured animals. Both MRcko and MR antagonist treatment stabilized damaged myofibers and increased collagen infiltration or compaction at 4 days post-injury. MR antagonist treatment also led to reduced myofiber size at 7 and 14 days post-injury. These data support that MR signaling contributes to the normal muscle repair process following acute injury. MR antagonist treatment delays muscle fiber growth, so temporary discontinuation of these drugs after a severe muscle injury could be considered.
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http://dx.doi.org/10.3389/fphys.2019.01324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830343PMC
October 2019

Acute Promyelocytic Leukemia in a Child With Dandy-Walker Malformation: A Rare Association.

J Pediatr Hematol Oncol 2020 01;42(1):81

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute Medanta-The Medicity Hospital, Gurgaon Haryana, India.

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http://dx.doi.org/10.1097/MPH.0000000000001655DOI Listing
January 2020

Multiple importations and transmission of colistin-resistant in a hospital in northern India.

Infect Control Hosp Epidemiol 2019 12 18;40(12):1387-1393. Epub 2019 Oct 18.

US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Objective: Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.

Design: Retrospective observational study.

Methods: Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.

Results: Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).

Conclusions: Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.
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http://dx.doi.org/10.1017/ice.2019.252DOI Listing
December 2019

Successful treatment of cytomegalovirus encephalitis post TCR-alpha-beta/CD19 depleted haploidentical stem cell transplant by unmanipulated donor lymphocyte infusions.

Pediatr Hematol Oncol 2019 11 2;36(8):520-522. Epub 2019 Oct 2.

Pediatric Hematology, Oncology & Bone Marrow Transplantation Unit, Cancer Institute, Medanta The Medicity, Gurgaon, Haryana, India.

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http://dx.doi.org/10.1080/08880018.2019.1663326DOI Listing
November 2019

Dengue Fever with Acute Disseminated Encephalomyelitis : Sensorium Imbroglio.

J Assoc Physicians India 2019 Oct;67(10):80-82

Professor, Department of Medicine, All India Institute of Medical Sciences, New Delhi.

Dengue is the most common arboviral disease affecting many countries worldwide. With endemicity of the disease and huge burden, atypical clinical presentations occur posing high diagnostic and therapeutic dilemma. Emerging neurological complications in dengue fever are reported in recent past Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination and characterized by multifocal white matter involvement. Early suspicion and diagnosis of such complication is clinical dilemma and it further complicates the clinical scenario. This case report highlights occurrence of such uncommon manifestation of ADEM in commonly occurring dengue fever along with its diagnosis and successful management in a young individual.
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October 2019

Langerhans Cell Histiocytosis Masquerading as Hypereosinophilia in a Child.

J Pediatr Hematol Oncol 2019 May;41(4):335-336

Department of Pediatric Hematology Oncology & BMT, Medanta The Medicity Hospital, Gurgaon, India.

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http://dx.doi.org/10.1097/MPH.0000000000001445DOI Listing
May 2019

Mineralocorticoid receptor antagonists improve membrane integrity independent of muscle force in muscular dystrophy.

Hum Mol Genet 2019 06;28(12):2030-2045

Department of Physiology and Cell Biology.

Mineralocorticoid receptor (MR) drugs have been used clinically for decades to treat cardiovascular diseases. MR antagonists not only show preclinical efficacy for heart in Duchenne muscular dystrophy (DMD) models but also improve skeletal muscle force and muscle membrane integrity. The mechanisms of action of MR antagonists in skeletal muscles are entirely unknown. Since MR are present in many cell types in the muscle microenvironment, it is critical to define cell-intrinsic functions in each cell type to ultimately optimize antagonist efficacy for use in the widest variety of diseases. We generated a new conditional knockout of MR in myofibers and quantified cell-intrinsic mechanistic effects on functional and histological parameters in a DMD mouse model. Skeletal muscle MR deficiency led to improved respiratory muscle force generation and less deleterious fibrosis but did not reproduce MR antagonist efficacy on membrane susceptibility to induced damage. Surprisingly, acute application of MR antagonist to muscles led to improvements in membrane integrity after injury independent of myofiber MR. These data demonstrate that MR antagonists are efficacious to dystrophic skeletal muscles through both myofiber intrinsic effects on muscle force and downstream fibrosis and extrinsic functions on membrane stability. MR antagonists may therefore be applicable for treating more general muscle weakness and possibly other conditions that result from cell injuries.
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http://dx.doi.org/10.1093/hmg/ddz039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548225PMC
June 2019

Clinico-microbiological profile of healthcare associated pneumonia in critically ill patients at level-I trauma centre of India.

J Lab Physicians 2018 Oct-Dec;10(4):406-409

Division of Trauma Surgery and Critical Care, JPNATC, AIIMS, New Delhi, India.

Introduction: Device-associated infections constitute the majority of health-care infections in Intensive Care Units (ICUs). Trauma patients are more prone to acquire such infections; ventilator-associated pneumonia (VAP) being the most common Health care associated infections (HAI) in ICU has serious implications such as increased morbidity, prolonged hospital stay, and mortality. This study aims to compare the clinicomicrobiological profile of VAP and non-VAP trauma patients at Level I trauma center.

Materials And Methods: A 4-year retrospective study of prospectively maintained database was conducted at Level 1 trauma center from January 2013 to December 2016. The patients were classified into two groups named VAP and non-VAP patients. VAP patients were defined according to the criteria of the Centers for Disease Control and Prevention. The data were compiled and analyzed. Statistical data were analyzed using SPSS version 21 software.

Results: During the study period, 134 (13%) cases of VAP and 909 (87%) non-VAP cases were observed in our study. The total number of ventilator days for VAP patients was 5128 days, which ranged from 2 to 82 days (median 42 days). The length of hospital stay in non-VAP category ranged from 1 to 390 days (median 195.5 days). Inhospital mortality was observed in 62 (46%) patients with VAP. Three hundred and eighteen (35%) non-VAP patients had also had a fatal outcome. Gram-negative organisms, most commonly spp. (13, 21%), were reported in the fatal VAP patients.

Conclusion And Discussion: Higher rate of mortality was observed in patients with VAP in comparison to non-VAP patients, both being on mechanical ventilation. Early recognition of VAP, implementation of proper VAP preventive bundle strategies, and stringent infection control practices are essential mandates to prevent VAP.
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http://dx.doi.org/10.4103/JLP.JLP_85_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210831PMC
December 2018

Erythema Nodosum Leprosum as a Rare and Challenging Cause of Pyrexia of Unknown Origin.

J Assoc Physicians India 2018 04;66(4):63-6

Professor Department of Medicine.

A 30-year old male presented with fever for last 1 year. There were associated multiple painful skin eruptions with hyperpigmentation and scaling over whole body which had been progressively increasing. He also had anasarca along with generalized weakness. He presented to us in shock after an acute episode of gastroenteritis. After stabilization, he was evaluated for cause of fever. Routine fever workup (for typhoid, syphilis, malaria, filariasis, HIV, scrub typhus, leishmaniasis) was negative. CECT chest and abdomen revealed hepatosplenomegaly. There was no response to intravenous (IV) antibiotics and anti-fungal medications. Slit skin smears revealed 3+ acid fast bacilli (AFB). Skin biopsy revealed fragmented acid-fast bacilli with dense collection of neutrophils and foamy histiocytes in upper and middle dermis suggestive of Erythema Nodosum Leprosum (ENL). A diagnosis of ENL with lepromatous leprosy was made and patient started on steroids and thalidomide and subsequently on multidrug therapy (MDT). On therapy, patient's symptoms improved, and skin lesions resolved. Though Leprosy itself is a well-known common cause of PUO in India, its first presentation as ENL is rare and needs good index of suspicion and timely management.
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April 2018

Epidemiological investigation and successful management of a Burkholderia cepacia outbreak in a neurotrauma intensive care unit.

Int J Infect Dis 2019 Feb 17;79:4-11. Epub 2018 Oct 17.

Department of Laboratory Medicine, Jai Prakash Narayan Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address:

Objective: The detailed epidemiological and molecular characterization of an outbreak of Burkholderia cepacia at a neurotrauma intensive care unit of a level 1 trauma centre is described. The stringent infection control interventions taken to successfully curb this outbreak are emphasized.

Methods: The clinical and microbiological data for those patients who had more than one blood culture that grew B. cepacia were reviewed. Bacterial identification and antimicrobial susceptibility testing was done using automated Vitek 2 systems. Prospective surveillance, environmental sampling, and multilocus sequence typing (MLST) were performed for extensive source tracking. Intensive infection control measures were taken to further control the hospital spread.

Results: Out of a total 48 patients with B. cepacia bacteraemia, 15 (31%) had central line-associated blood stream infections. Two hundred and thirty-one environmental samples were collected and screened, and only two water samples grew B. cepacia with similar phenotypic characteristics. The clinical strains characterized by MLST typing were clonal. However, isolates from the water represented a novel strain type (ST-1289). Intensive terminal cleaning, disinfection of the water supply, and the augmentation of infection control activities were done to curb the outbreak. A subsequent reduction in bacteraemia cases was observed.

Conclusion: Early diagnosis and appropriate therapy, along with the rigorous implementation of essential hospital infection control practices is required for successful containment of this pathogen and to curb such an outbreak.
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http://dx.doi.org/10.1016/j.ijid.2018.10.008DOI Listing
February 2019

Uncommon manifestation of leptospirosis: a diagnostic challenge.

BMJ Case Rep 2018 Oct 7;2018. Epub 2018 Oct 7.

Professor, Department of Medicine, All India Institute of Medical Sciences, New Delhi.

Leptospirosis is a zoonotic disease commonly affecting the tropical countries. It may have protean clinical manifestations including hepatorenal dysfunction, myocarditis, pulmonary haemorrhage, meningitis, optic neuritis and rhabdomyolysis. Neurological manifestation of leptospirosis without the classical hepatorenal dysfunction is a rare entity. This complication of leptospirosis can present with diverse central and peripheral neurological presentations. The overlapping clinical manifestations with many common tropical pathogens often pose diagnostic dilemma and delay in definitive therapy may lead to adverse clinical consequences. We report a case of a 19-year-old man with no prior comorbidities presenting with high-grade fever and altered sensorium. He was diagnosed to be a probable case of leptospirosis, based on all available test results and by fulfilment of parameters under modified Faine's criteria. The patient was successfully managed and discharged in stable condition.
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http://dx.doi.org/10.1136/bcr-2018-225281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194365PMC
October 2018

Unusual presentation of syncytial variant of nodular sclerosis classical Hodgkin's lymphoma presenting as unilateral lung mass in a 15-year-old child.

Acta Oncol 2018 12 13;57(12):1729-1732. Epub 2018 Aug 13.

a Department of Pathology, Lab Medicine and Transfusion Medicine , Medanta - The Medicity Hospital , Gurgaon , India.

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http://dx.doi.org/10.1080/0284186X.2018.1502465DOI Listing
December 2018

Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide for Hemophagocytic Lymphohistiocytosis.

J Pediatr Hematol Oncol 2019 Apr;41(3):e158-e160

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Fortis Memorial Research Institute.

Allogeneic hematopoietic stem cell transplant (HSCT) has been known to be a curative therapy for patients with hemophagocytic lymphohistiocytosis (HLH) but donor availability is an issue. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) has been investigated as a feasible option for various malignant and nonmalignant conditions with reduced incidence of acute graft versus host disease (GVHD) and graft rejection. However, its use has not been described in children with HLH and here we describe 2 boys who underwent successful haploidentical HSCT with PTCy. None had acute GVHD and 1 had limited chronic GVHD. Both are alive and disease-free at follow-up of 912 and 239 days, respectively. Haploidentical HSCT with PTCy is a feasible option for children with HLH lacking a matched sibling donor.
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http://dx.doi.org/10.1097/MPH.0000000000001265DOI Listing
April 2019

Mineralocorticoid Receptor Antagonists in Muscular Dystrophy Mice During Aging and Exercise.

J Neuromuscul Dis 2018;5(3):295-306

Department of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, OH, USA.

Background: Mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors have shown preclinical efficacy for both skeletal and cardiac muscle outcomes in young sedentary dystrophin-deficient mdx mice also haploinsufficient for utrophin, a Duchenne muscular dystrophy (DMD) model. The mdx genotypic DMD model has mild pathology, making non-curative therapeutic effects difficult to distinguish at baseline. Since the cardiac benefit of mineralocorticoid receptor antagonists has been translated to DMD patients, it is important to optimize potential advantages for skeletal muscle by further defining efficacy parameters.

Objective: We aimed to test whether therapeutic effects of mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors are detectable using three different reported methods of exacerbating the mdx phenotype.

Methods: We tested treatment with lisinopril and the mineralocorticoid receptor antagonist spironolactone in: 10 week-old exercised, 1 year-old sedentary, and 5 month-old isoproterenol treated mdx mice and performed comprehensive functional and histological measurements.

Results: None of the protocols to exacerbate mdx phenotypes resulted in dramatically enhanced pathology and no significant benefit was observed with treatment.

Conclusions: Since endogenous mineralocorticoid aldosterone production from immune cells in dystrophic muscle may explain antagonist efficacy, it is likely that these drugs work optimally during the narrow window of peak inflammation in mdx mice. Exercised and aged mdx mice do not display prolific damage and inflammation, likely explaining the absence of continued efficacy of these drugs. Since inflammation is more prevalent in DMD patients, the therapeutic window for mineralocorticoid receptor antagonists in patients may be longer.
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http://dx.doi.org/10.3233/JND-180323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732783PMC
November 2018